title: Deficiency of the hexosaminidase A activator protein in a case of GM2 gangliosidosis; variant AB.
abstract: A patient is described whose clinical course and pathologic features, including massive brain storage of GM2 ganglioside in grey matter, are identical with those of classical Tay-Sachs disease despite normal levels of beta -N-acetyl hexosaminidase and normal isozyme distribution. The kinetic properties and thermolability of the patient's hexosaminidase are normal. Crude extracts of a postmortem sample of patient's liver can catalyze the hydrolysis of 5.1 pmoles of labeled GM2 ganglioside/16 h/mg of protein (control liver = 69.9 pmoles/16 h/mg). Addition of partially purified human liver hexosaminidase A activator protein stimulated the hydrolysis of substrate by the patients liver extract by 27-fold compared to 3-fold for control livers. Measurement of "activator" in enriched fractions of patient's and control liver showed a reduced (25-30% of control) amount of stimulation of hexosaminidase A catalyzed hydrolysis of GM2 ganglioside as well as of Asialo-GM2 ganglioside. The addition of sphingomyelin to reaction mixtures, which is known to inhibit surfactant stimulation of hexosaminidase A, reduced activation of hexosaminidase A by patient's liver preparation to undetectable levels. Polyacrylamide gel electrophoresis of enriched preparations of control and patient's liver showed a rapidly migrating protein band in control liver corresponding to the activator protein and the absence of this protein band in the patient's liver.
mesh_terms: D001921:Brain / Q000201:enzymology / Q000378:metabolism; D001923:Brain Chemistry; D005678:G(M2) Ganglioside / Q000378:metabolism*; D005732:Gangliosides / Q000032:analysis / Q000378:metabolism*; D005733:Gangliosidoses / Q000378:metabolism*; D006023:Glycoproteins; D006596:Hexosaminidases / Q000378:metabolism; D006801:Humans; D007223:Infant; D008099:Liver / Q000201:enzymology / Q000378:metabolism; D008110:Liver Extracts / Q000494:pharmacology; D008247:Lysosomes / Q000201:enzymology; D008297:Male; D011488:Protein Deficiency / Q000378:metabolism; D049231:Saposins; D049128:Sphingolipid Activator Proteins
chemical_list: D005732:Gangliosides; D006023:Glycoproteins; D008110:Liver Extracts; C483345:PSAP protein, human; D049231:Saposins; D049128:Sphingolipid Activator Proteins; D005678:G(M2) Ganglioside; D006596:Hexosaminidases